The gene consists of 7 exons that span approximately 12 kb of genomic DNA in the centromere-to-telomere orientation. The translation initiation codon and the stop codon are predicted to exon 1 and exon 7, respectively.

Transcription

The corresponding "wildtype" mRNA transcript is 3.6 kb.

Protein

Description

The open reading frame is predicted to encode an 1127 amino acid protein with an estimated molecular weight of 120 kDa.

Expression

Northern blot analysis has indicated that the normal expression of the NUT gene is highly restricted to the testis. No investigations have yet been made at the protein level.

Carcinoma with t(15;19) translocation is invariably fatal with a rapid clinical course when located to the midline thoracic, head and neck structures. One tumor, displaying the cytogenetic and molecular cytogenetic features of carcinoma with t(15;19) translocation, but located to the iliac bone has been reported successfully cured. It has been suggested that a critical prognostic difference exists between BRD4-NUT/t(15;19) positive tumors and tumors where NUT is rearranged but fused to an as yet unknown partner.

Cytogenetics

t(15;19)(q14;p13) [reported breakpoints: t(15;19)(q11-15;p13)].

Hybrid/Mutated Gene

The t(15;19)(q14;p13) results in an BRD4-NUT chimeric gene where exon 10 of BRD4 is fused to exon 2 of NUT.

Abnormal Protein

The BRD4-NUT fusion is composed of the N-terminal of BRD4 (amino acids 1-720 out of 1372) and almost the entire protein sequence of NUT (amino acids 6-1127). The N-terminal of BRD4 includes bromodomains 1 and 2 and other, less well characterized functional domains.

Oncogenesis

It has been suggested that the oncogenic effect of the NUT-BRD4 fusion is caused not only by the abnormal regulation of NUT by BRD4 promoter elements but also by the consequent ectopic expression of NUT in non-germinal tissues.

Breakpoints

Note

The vast majority of reported breakpoints in carcinoma with t(15;19) translocation were assigned to band 19p13, the exception being the cytogenetic interpretation of a 19q13 breakpoint reported once. The reported breakpoints on chromosome 15 have varied (15q11-q15).

Bibliography

Midline carcinoma with t(15;19) and BRD4-NUT fusion oncogene in a 30-year-old female with response to docetaxel and radiotherapy.